Dried blood spot sampling of nilotinib in patients with chronic myeloid leukaemia: a comparison with venous blood sampling
Dried blood spot sampling of nilotinib in patients with chronic myeloid leukaemia: a comparison with venous blood sampling
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DOI：
10.1111/jphp.12757
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发表时间：
2017-10-01
影响因子：
3.3
通讯作者：
Swart, Eleonora L.
中科院分区：
文献类型：
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作者：
Boons, Christel C. L. M.;Chahbouni, Abdel;Swart, Eleonora L.
目的比较慢性粒细胞白血病(CML)患者静脉采血和干血斑(DBS)血药浓度。探讨如何根据血药浓度预测尼洛替尼的血药浓度。方法采集20例患者的血药浓度和静脉血样40份。用手指刺法采集毛细血管血，斑点于DMPK-C Whatman采样纸上，同时采集静脉血。用三种方法从DBS浓度预测血浆浓度：(1)个体和(2)平均红细胞压积校正和(3)血浆和DBS浓度之间的偏差。尼洛替尼血药浓度范围为376~2663g/L，DBS浓度范围为144~1518g/L，斜率为0.56(95%CI，0.51~0.61)，截距为-41.68g/L(95%CI，-93.78~10.42)。血药浓度计算值与实测值的平均偏差分别为-14.3%(方法1)、-14.0%(方法2)和-0.6%(方法3)，分别有73%、85%和80%的样品的计算结果与实测值相差在20%以内。斜率分别为0.96(95%CI，0.86~1.06)、0.95(95%CI，0.86~1.03)和1.00(95%CI，0.91~1.09)。DBS取样评估慢性粒细胞白血病患者的尼洛替尼浓度似乎是一种适合静脉取样的选择。
ObjectivesTo compare nilotinib concentrations obtained by venous blood sampling and dried blood spot (DBS) in patients with chronic myeloid leukaemia (CML). It was investigated how to predict nilotinib plasma levels on the basis of DBS.MethodsForty duplicate DBS and venous blood samples were collected from 20 patients. Capillary blood was obtained by finger prick and spotted on DMPK-C Whatman sampling paper, simultaneously with venous blood sampling. Plasma concentrations were predicted from DBS concentrations using three methods: (1) individual and (2) mean haematocrit correction and (3) the bias between plasma and DBS concentrations. Results were compared using Deming regression and Bland-Altman analysis.Key findingsNilotinib plasma concentrations ranged from 376 to 2663g/l. DBS concentrations ranged from 144 to 1518g/l. The slope was 0.56 (95% CI, 0.51 to 0.61) with an intercept of -41.68g/l (95% CI, -93.78 to 10.42). Mean differences between calculated and measured plasma concentrations were -14.3% (method 1), -14.0% (method 2) and -0.6% (method 3); differences were within 20% of the mean in 73%, 85% and 80% of the samples, respectively. The slopes were respectively 0.96 (95% CI, 0.86 to 1.06), 0.95 (95% CI, 0.86 to 1.03) and 1.00 (95% CI, 0.91 to 1.09).ConclusionsPlasma concentrations of nilotinib could be predicted on the basis of DBS. DBS sampling to assess nilotinib concentrations in CML patients seems a suitable alternative for venous sampling.